Aminoalkylphosphinic acids



United States Patent 3,332,987 AMINOALKYLPHOSPHINIC ACIDS Ivan C. Popoif, Ambler, Burton Peter Block, Wayne, and

Ludwig K. Huber, Philadelphia, Pa., assignors to Pennsalt Chemicals Corporation, Philadelphia, Pa., a corporation of Pennsylvania No Drawing. Filed June 24, 1963, Ser. No. 290,234 3 Claims. (Cl. 260--500) This invention relates to novel phosphine oxides and phosphinic acids having the structure where R is a hydrocarbon containing from one to ten carbon atoms selected from the group consisting of alkyl and aryl, R is a member selected from the group consisting of hydroxyl, alkyl and aryl containing from one to ten carbon atoms, and R is a member of the group consisting of hydrogen and lower alkyl. The compounds of this invention are useful chelating agents.

When R in'the above formula is alkyl or aryl as defined, the compound is an a-aminoalkylphosphine oxide. On the other hand, when R is hydroxyl, the compound is an -aminoalkylphosphinic acid. Both the phosphine oxides and phosphinic acids of the invention are prepared by hydrolysis of the corresponding phthalimidomethylphosphine oxides and phosphinates, which compounds have the structure where R and R are as defined above for the compounds of this invention and R is selected from the group consisting of hydroxy, alkyl, aryl, alkoxy and aryloxy containing from one to ten carbon atoms. These phthalimidomethyl phosphorus compounds are the subject matter of Serial No. 290,245 filed of even date herewith and now US. Patent No. 3,222,378.

The intermediate phthalimidoalkyl compounds of the invention where R is hydrogen are prepared by reaction of an N-bromomethylphthalimide with the appropriate phosphinite or phosphonite whereby an alkyl bromide is eliminated. Thus, for example, the N-bromomethylphthalimide may be heated with an alkyl phosphinite without a solvent or in an organic solvent system such as xylene, toluene, etc. to obtain a reaction as follows:

When R of the phthalimidoalkyl compound is a lower alkyl such as methyl, ethyl, propyl and butyl, the inter- 3,332,987 Patented July 25, 1967 mediate phthalimidoalkyl compound is prepared by reaction .of a phosphonite or phosphinite with an N(a-halo alkyl)phthalimide, viz:

ll C Appropriate phosphinites useful for making the phthalimidoalkylphosphine oxide intermediates will include methyl methyl (phenyl)phosphinite, butyl butyl(phenyl)- phosphinite, methyl dinaphthylphosphinite, methyl naphthyloctylphosphinite, methyl naphthylphenylphosphinite, g methyl didecylphosphinite, and the. like. As indicated,

. instead of using a phosphinite to react with the N-a-haloalkylphthalimide, a phosphonite may 'be used to obtain phosphinates. Appropriate phosphonites may be prepared in accordance with the procedure of G. Kamai; Zhur. Obshchei. Khim.,'vol. 18, p. 443 (1948), and will include such compounds as dimethyl phenylphosphonite, diethyl phenylphosphonite, dibutyl phenylphosphonite, methyl phenyl phenylphosphonite, diethyl naphthylphos phonite, dimethyl octylphosphonite, and the like. As indicated, the preparation of the intermediate phthalimidoe alkyl phosphorus compound is carried out by reaction of the N-a-haloalkylphthalimide with the appropriate phosphorus compounds by heating the reactants and removing the alkyl bromide formed. The general procedure for this reaction involves contacting essentially stoichiometric amounts of the reagents under nitrogen with or without a solvent medium, at atmospheric or reduced pressures and at temperatures on the order of about 0 to C. higher than the temperature at which the alkyl halide byproduct begins to form. As the reaction proceeds the alkyl halide by-product is removed from the reaction zone, preferably by applying vacuum, and if desired, this byproduct may be condensed in a Dry Ice trap. The vacuum applied will vary considerably depending upon the volatility of the alkyl halide, but will normally be in the order of 300 to 500 mm. When the alkyl halide is no longer generated, it is assumed that the reaction is complete and heating may be discontinued shortly thereafter. The proudct in the reaction flask is the phthalimidoalkyl phosphorus compound and may be purified by crystallization or distillation in accordance with normal procedures. To obtain the aminoalkyl compound of this invention, the phthalimidoalkyl phosphorus compounds are hydrolyzed with a mineral acid, preferably by using an excess of aqueous HBr, and the hydrolysis is carried out at a temperature of about 65 to 130 C. When the hydrolysis is car ried out with a phthalimidomethyl phosphinate, both the phthaloyl group and the alkoxy group (i.e., R are hydrolyzed, although the alkoxy group is hydrolyzed first. 65 The products of the invention are colorless crystalline materials with sharp melting points when pure. The phosphine oxides of the invention are soluble in organic sol-' vents such as ketones (acetone), aromatic hydrocarbons (benzene, toluene, etc.), alcohols (ethanol, methanol, 70 etc.) and water, and also show some slight solubility in hot aliphatic hydrocarbons, such as n-hexane. The phosphinic acids of the invention are likewise solid, colorless, crystalline materials and are generally insoluble in organic solvents such as benzene, ethanol and n-hexane. On the other hand, the phosphinic acids show solubility in water and in aqueous solution have an acid reaction.

The following examples will serve to more fully illustrate the invention.

EXAMPLE 1 Diphenyl(phthalimidomethyhphosphine oxide is ob- ;ained by reaction of equimolar amounts of N-bromomethylphthalimide and methyl diphenylphosphinite in rylene. The reaction mixture is refluxed at atmospheric Jressure for 7 hours under a stream of nitrogen and 92% of the methyl bromide is collected in a Dry Ice rap. In this way, 88.6% of the crude product precipitates 1nd is recrystallized from dioxane. The product is soluble n acetone and ethanol, insoluble in benzene, ether, l-hexane, water and xylene, and melts at 206-2065" C. ound: 69.31% C, 4.18% H, 3.85% N and 8.64% P; :alculated for C H NO P: 69.80% C, 4.43% H, 3.88% I and 8.60% P.

Aminmethyl(diphenyl)ph0sphine oxide having the itructure ll HgN-CHg-li-CgHs 5 obtained by the hydrolysis of diphenyl(phthalimidonethyl)phosphine oxide with 48% aqueous HBr, which achieved by refluxing for hours. The mass is then lltered to remove phthalic acid and the filtrate is evapoated. The residue containing the crude hydrobromide is issolved in water and, after addition of an excess of odium carbonate, is evaporated to dryness. The comletely dry evaporation residue is extracted with n-hexane 1 a Soxhlet to recover the pure product melting at 01.5-102.5 C. The product is very hygroscopic, soluble 1 acetone, benzene, ethanol and water and slightly sol- .ble in hot n-hexane. It can be sublimed at about 100 C. ath temperature under reduced pressure of 0.05 mm. "he infrared spectrum of the product confirms the presnce of NH P-aO, and PC H bonds. Found: 7.54% C, 6.23% H, 5.40% N, and 13.38% P; calculated )1 C H NOP: 67.50% C, 6.15% H, 6.06% N and 3.38% P.

EXAMPLE 2 Ethyl phmyl(phthalimidomethyl)phosphinate is preared by adding N-bromomethylphthalimide to diethyl henylphosphonite in xylene. The addition lasts 6 hours 'hile refluxing at reduced pressure of about 300 mm. he by-product, ethyl bromide, is collected in 93.5% yield. he reaction mixture is cooled at 5 C. and filtered t0 olate 98% of crude product melting at 105-109 C. The ure product, melting at 111-113" C., is obtained in 86% ield by recrystallization from a 1:1 mixture of benzene 1d n-hexane. It is soluble in acetone, benzene, and hanol, and insoluble in n-hexane and water. Found: 2.00% C, 4.86% H, 4.25% N and 9.43% P; calculated 1r C H NO P: 61.99% C, 4.33% H, 4.48% N and 54% P.

Amin0methyl(phenyl)phosphinic acid was prepared in :cordance with the details of Example 1 by the hydrol- ElS of ethyl phenyl(phthalimidomethyl)phosphinate with ueous HBr. The solid evaporation residue of the hy- 'olysis reaction mixture has a melting point of 183-190 (with HBr evolution). Analysis of the residue indiites 30.54% Br for the amine hydrobromide. Calculated 11116 for the amine hydrobromide is 31.7% Br. The resi- 1e is refluxed for 30 hours in alcohol containing aniline an amount equivalent to the HBr content. The solid filtered olf at about 20 C. to obtain 95% crude prod- :t (M.P. 265-268 C.) and is purified by recrystallizaan from 75% aqueous ethanol. The pure aminomethyl- 4 (phenyDphsphinic acid yield) has a melting point of 285.5-286.5 C. (decomposition) and is insoluble in benzene, ethanol and n-hexane. Its 0.01 molar aqueous solution has a pH of 4.5. Its infrared spectrum shows absorptions for P O, PC H P-OH and NH and strong H-bonding due to inner salt formation. Found: 49.10% C, 5.83% H, 8.30% N and 17.70% P; calculated for C H NO Pz 49.06% C, 5.85% H, 8.18% N and 18.10% P.

EXAMPLE 3 a-Am inoethyKphenyl)phosphinio acid of structure is obtained by reaction of dimethyl phenylphosphonite with N(a-chloroethyl)phthalimide and subsequent hydrolysis of the intermediate without isolation. The formation of methyl chloride is noticed at C. and the reaction is carried out at C. 80% of the theoretical amount of methyl chloride is collected indicating the formation of methyl a-phthalimidoethyl(phenyl)phosphinate. The crude reaction mixture is hydrolyzed with 48% aqueous HBr. The viscous evaporation residue of the hydrolysis is refluxed with acetone containing equimolar amounts of aniline (based on theoretical yield). A solid precipitates and is repeatedly recrystallized from 95 aqueous ethanol to yield the pure a-aminoethyl(phenyl)phosphinic acid melting at 265 C. The product is soluble in water and insoluble in acetone, benzene, ether and n-hexane; its infrared spectrum shows absorptions for PC H P-OH, P-e O, -NH and strong H-bonding due to inner salt formation. Its 0.01 molar aqueous solution has a pH of 4.6. Found: 51.35% C, 6.24% H, 7.75% N and 16.24% P; calculated for C H NO P: 51.89% C, 6.54% H, 7.76% N and 16.73% P.

EXAMPLE 4 Hydrolysis and work-up in accordance with the details of Example 2 of methyl phenyl(phthalimidomethyl)phosphinate and phenyl(phthalimidomethyl)phosphinic acid result in excellent yields of aminomethyl(phenyl)phosphinic acid.

EXAMPLE 5 Ethyl methyl(phthalimidomethyl)phosphinate is prepared by reaction of diethyl methylphosphonite with N- bromomethylphthalirnide in xylene. The reaction mixture is kept for 4 hours at 70-80 C. at reduced pressure of about 300 mm. and 99% of the theoretical ethyl bromide is collected. Upon filtration at 10 C., 99% of the crude product, M.P. 99-105 C., is obtained and is recrystallized from a 1:1 mixture of benzene and n-hexane to recover 92% of ethyl methyl(phthalimidomethyl)phosphinate melting at 109-111" C. It is soluble in acetone, carbon tetrachloride, ethanol, ether and methanol and insoluble in n-hexane. Its infrared spectrum confirms the presence of P O, POC and C(O)N Found: 53.40% C, 4.78% H, 5.05% N and 11.20% P; calculated for C H NO P: 53.93% C, 5.28% H, 5.24% N and 11.59% P. Hydrolysis with aqueous HBr as in Example 1 results in excellent yields of aminomethyl(methyl)phosphinic acid which, when crystallized from 66% ethanol, melts at 296298 C. and is soluble in water and methanol and slightly soluble in ethanol, and insoluble in benzene. Its 0.01 molar aqueous solution has a pH of 4.8. Analysis: Found: 22.00% C, 6.80% H, 12.71% N, 28.28% P; calculated for C H NO P: 22.02% C, 7.39% H, 12.84% N and 28.41% P.

hydrolyzed with aqueous HBr, aminomethyl(dioctyl) phosphine oxide is obtained in excellent yield. 7

EXAMPLE 7 Hydrolysis of dimethyl(phthalimidomethyl)phosphine oxide yields aminomethyl(dimethyl)phosphine oxide.

EXAMPLE 8 NH CH P (O) (OH)C H in 10 ml. of water. The addition of ethyl alcohol precipitated a white solid. The solid was washed with ethyl alcohol and dried; it weighed 0.77 g. and melted at 325 C. Chemical analysis and infrared spectral analysis of this compound clearly show that it is a chelateformulated as This chelate is stable to 330 C. on the thermobalance which is substantially better thermal stability than that exhibited by Zn(CI-I COCHCOCH which decomposes at 191 C. Thus the aminomethyl(phenyl)phosphinic acid is a ligand used for making coordination compounds having increased thermal stability. Such chelating compounds are also of value for chemical analysis of coordinating metals.

In similar manner, when dioxane is added to a solution of 2 g. of Zn(OCOCH -2H O and 2.0 g. of NH CH P(O)(OH)CH in aqueous alcohol, the chelate ZN [O P-(CH )CH NH is precipitated.

It will be understood that numerous changes and variations may be made from the above description and examples without departing from the spirit and scope of the invention.

We claim:

1. Compounds having the structure HzN-CH-%-R1 where R is an alkyl group containing from 1 to 10 carbon atoms.

2. Aminomethyl(methyl)phosphinic acid. 3. Aminomethyl(ethyl)phosphinic acid.

References Cited Ka-bachnik et al., Chem. Abstracts, vol. (1956) p. 219.

LEON ZITVER, Primary Examiner.

J. E. EVANS, Assistant Examiner. 

1. COMPOUNDS HAVING THE STRUCTURE
 2. AMINOMETHYL(METHYL)PHOSPHINIC ACID.
 3. AMINOMETHYL(ETHYL)PHOSPHINIC ACID. 